Depressed patients

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

Selected for clinical trials as a compound to calm agitated patients, imipramine was relatively ineffective. However, it was observed to be effective in the treatment of certain depressed patients (38). Early studies on the mechanism of action showed that imipramine potentiates the effects of the catecholamines, primarily norepinephrine. This finding, along with other evidence, led to the hypothesis that the compound exerts its antidepressant effects by elevating norepinephrine levels at central adrenergic synapses. Subsequent studies have shown that the compound is a potent inhibitor of norepinephrine reuptake and, to a lesser extent, the uptake of serotonin, thus fitting the hypothesis that had been developed to explain the antidepressant actions ofMAOIs. 

Sevarino KA, Oliveto A, Kosten TR Neurobiological adaptations to psychostimulants and opiates as a basis of treatment development. Ann N Y Acad Sci 909 51 —87,2000 Silberman EK, Reus VI, Jimerson DC, et al Heterogeneity of amphetamine response in depressed patients. AmJ Psychiatry 138 1302—1307, 1981 Sofuoglu M, Brown S, Babb DA, et al Depressive symptoms modulate the subjective and physiological response to cocaine in humans. Drug Alcohol Depend 63 131-137, 2001... 

Briggs G, Freeman R, Yaffe S Drugs in Pregnancy and Lactation A Reference Guide to Maternal and Fetal Risk. Philadelphia, Lippincott, Williams Wilkins, 2002 Chengappa KN, Kambhampati R, Perkins K, et al Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on neatment with selective serotonin reuptake inhibitor antidepressants. J Clin Psychiatry 62 503—508, 2001... 

Such difficulties prompted research workers to look for some other index of NT function in humans. These range from studies on platelets, such as abnormalities in their amine uptake and MAO activity in depressed patients, to changes in the secretion of a hormone known to be controlled by a particular NT. Thus if NA controls growth hormone release, and the secretion of the hormone is changed in depressed patients, does that confirm a role for NA in the mediation of depression ... 

Measurements in depressed patients compared with normal subjects, euthymic controls or patients suffering from an unrelated psychiatric disorder. NCC No consistent change. The changes indicated are based on the most frequently published findings. 

Also, a high proportion of depressed patients do not show the reduction in cortisol secretion which is seen when normal subjects are challenged with the synthetic glucocorticoid, dexamethasone, that normally decreases further release through feedback... 

Heninger, G. Chamey, D.S. and Sternberg, D.E. Serotonergic function in depression Prolactin response to intravenous tryptophan in depressed patients and healthy subjects. Arch Gen Psychiatry 41 398-402. 1984. 

Plasma prolactin changes following fenfluramine in depressed patients compared to controls An evaluation of central serotonergic responsivity in depression. Life Sci 34 1029-1039, 1984. 

Van Praag, H.M. Schut, T. Bosma, E. and Van Den Bergh, R. A comparative study of the therapeutic effects of some 4-chlorinated amphetamine derivatives in depressive patients. Psychopharmacologia 20 66-76, 1971. 

Occasionally, severely depressed patients also will present I with psychotic symptoms ... 

The obvious goal of therapy for the depressed patient is the resolution of depressive symptoms and a return to euthymia. Once symptoms have resolved, then the purpose of ongoing therapy is to prevent relapse and recurrence of depressive symptoms. One extremely important outcome in the treatment of MDD is the prevention of suicidal attempts. Other essential outcomes include improvement of the patient s quality of life, normalization of functioning in areas such as work and relationships, avoidance or minimization of adverse effects, and reduction of health care costs.15... 

The initial dose of SSRI is similar to that used in depression. Patients should be titrated as tolerated to response. Many patients will require maximum recommended daily doses. Patients with comorbid panic disorder should be started on lower doses (Table 37-4). When discontinuing SSRIs, the dose should be tapered slowly to avoid withdrawal symptoms, with the possible exception of fluoxetine. Relapse rates may be as high as 50%, and patients should be monitored closely for several weeks.58 Side effects of SSRIs in SAD patients are similar to those seen in depression and most commonly include nausea, sexual dysfunction, somnolence, and sweating. 

Arias, B., Catalan, R. et al. (2003). 5-HTTLPR polymorphism of the serotonin transporter gene predicts non-remission in major depression patients treated with citalopram in a 12-weeks follow up study. /. Clin. Psychopharmacol, 23(6), 563-7. 

Yoshida, K., Ito, K. etal. (2002). Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26(2), 383-6. 

Mendlewicz, J., Verbanck, P., Linkowski, P. Wilmotte, J. (1978). Lithium accumulation in erythrocytes of manic-depressive patients an in vivo twin study. Br. J. Psychiatry, 133,436-44. 

Marcos, L. R. Cancro, R. (1982). Pharmacotherapy of Hispanic depressed patients clinical observations. Am. J. Psychother., 36, 505-12. 

Priebe, S. (1987). Early subjective reactions predicting outcome of hospital treatment in depressive patients. Acta Psychiatr. Scand., 76, 134-8. 

Chinese depressed patients appeared to require lower dosages, with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy (Ng et al, 2006). Again, this finding has supported the fact that Asian patients, especially Chinese, need lower doses of antidepressant drugs than their Western counterparts. 

Furukawa, T. A., Kitamura, T. Takahashi, K. (2000). Treatment received by depressed patients in Japan and its determinants naturalistic observation from multi-center collaborative follow-up study. /. Affect. Disord., 60(3), 173-9. 

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